Role of Microbiota in Carcinogenesis and Cancer Treatment

Human body has around 30 trillion human cells, but microbiome in human body is constituted by estimated 39 trillion microbial cells including bacteria, viruses and fungi that live on and in us. They make up about 1-3 per cent of our total body mass but have huge potential implications on physiology and diseases. We now have plenty of literature that demonstrates an association between disruptions in the homeostasis of microbial communities (termed as dysbiosis) and varied pathologic conditions. In addition, there is a link between the disruption of commensal microbiota and carcinogenesis, including compelling evidence regarding the role of the gastrointestinal (gut) microbiota in modulating responses to cancer immunotherapy and data demonstrating that the microbial communities within the tumor microenvironment can contribute to therapeutic efficacy.

Gut dysbiosis and cancer development

There is evidence supporting that generalized dysbiosis of the gut microbiota may contribute to carcinogenesis. An association between repeated courses of antibiotics and the development of a variety of both gastrointestinal (GI)-tract and non-GI-tract tumors has been demonstrated in large case-control studies. The mechanisms through which dysbiosis is proposed to affect tumorigenesis and/or tumor growth across cancer types are varied (Fig. 1). The role of microbiota in genesis of colon, breast, liver/biliary tract and stomach is being investigated and is linked to various mechanisms. Comprehensive insights are lacking at the moment but studies are underway to better understand pathways; how gut microbes may influence carcinogenesis?

The gut microbiota and cancer therapy

Different types of gut microbiota ‘signatures’ exist in patients who respond to cancer treatment. These favorable signatures are associated with enhanced systemic immunity and intratumoral immune infiltrates. Additionally, many studies have demonstrated that the ‘responder’ and ‘nonresponder’ phenotypes could be recapitulated in germ-free or antibiotic-treated mouse models via fecal microbiota transplant (FMT)—and that manipulation of the gut microbiota with specific bacterial taxa could enhance therapeutic responses. In addition, there is now evidence that the gut microbiota may shape responses to other forms of cancer therapy including chemotherapy and targeted therapy.

On the other hand Chemotherapy can cause profound dysbiosis and affect multiple metabolic pathways. Antibiotics are frequently prescribed during the course of chemotherapy that also impact the microbiota; this is important, as concurrent antibiotic administration has now in several studies been shown to negatively impact the outcomes of cancer immunotherapy. In addition to modulating treatment responses the differential microbiome signatures are also associated with differential cancer therapeutic toxicities in different individuals such as development of graft versus host disease (GVHD) in allotransplant candidates.

The microbiome as a therapeutic target in cancer therapy

The famous Hippocrates quote “Let food be thy medicine and medicine be thy food,” recorded around 431 bc supports the notion of food and the gut microbiota to mediate many benefits within the human body. Efforts are currently underway to enhance therapeutic responses and/or decrease treatment-associated toxicity via modulation of the gut microbiota. FMT was originally used roughly 2,000 years ago when Chinese researchers orally administered ‘yellow soup,’ a slurry of stool from a healthy individual, to patients to cure them of severe dysentery. Within last decade, FMT has been more widely used in managing refractory GVHD, checkpoint inhibitors related colitis and clostridium difficile diarrhea.

Next generation biotherapeutics involving single or multistrain bacterial consortia, with strong scientific rationale and evidence regarding their efficacy are being investigated and developed. These are different from over-the-counter probiotic formulations, which are often considered to be supplements or ‘functional foods’. This field is young, and we are left with many unanswered questions. Multifaceted strategies are needed to monitor and modulate these factors to optimize health and to effectively treat diseases like cancer.

Keytake away-microbiome is the undiscovered organ of human body. It’s pertinent to maintain homeostasis of our microbiome by practicing healthy habits so as to keep at bay the various pathological conditions.

Dr. Manish Sharma
Consultant – Medical Oncology
RGCIRC, Niti Bagh